tbuckley/cabot-search huggingface dataset:
Real-world (RW) prevalence of adverse events (AEs) among patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Umang Swami, Bin Xie, Krishnan Ramaswamy, Nader N. El-Chaar, Wei Gao, Hongbo Yang, Yao Wang, Christopher Young, Lisa Mucha
Journal: Journal of Clinical Oncology (2023)

109 Background: Treatment options for mCSPC patients include adding novel hormonal therapy (NHT) with/without docetaxel (DOC) to androgen deprivation therapy (ADT). Uptake of these agents has been slow, and safety concerns may contribute to therapeutic inertia. This study aims to understand the RW occurrence of prespecified AEs among pts with mCSPC in the US. Methods: Claims from the PharMetrics Plus database (IQVIA, Durham, NC) were used to retrospectively estimate the proportion of pts with AEs among those with mCSPC from Jan 2014 through Jun 2021. Common AEs (≥10%) specified in FDA labels of treatments of interest or clinical trials ≥2% more prevalent than ADT alone were included in the study. Results of four clinically important AEs (fatigue, hot flash, sexual function and gastrointestinal [GI] AEs) are reported here. The proportions of pts with each of these AEs at specific timepoints plus 95% confidence intervals (CI) were estimated from cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting across ADT alone, ADT+ nonsteroidal antiandrogen (NSAA), ADT+DOC and ADT+NHT. Results: The mean age of the overall study population (N=4145) was 66 years. At baseline, common sites of metastasis were bone only (n=1886, 45.5%) and node only (n=1237, 29.8%); the most common medications used were for pain (n=2182, 52.6%) and corticosteroids (n=1213, 29.3%). The reference group for all comparisons of AEs was ADT alone. For the entire study period, GI AEs and fatigue were significantly higher only in the ADT+DOC group ( P&lt;0.001). Hot flash was higher in ADT+NHT ( P=0.05) and the ADT+DOC groups ( P&lt;0.001). No statistically significant differences in sexual function AEs in the groups was noted. The table shows the proportions of pts with specified AEs. Conclusions: In this large RW study, all groups, including ADT alone, showed an increase in AE reporting over time. Most AE rates with ADT+NHT were comparable to ADT alone and ADT+NSAA, while ADT+DOC showed an increase in GI AEs, fatigue and hot flash. [Table: see text]
Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Long-term follow-up from the JAVELIN Bladder 100 trial in subgroups defined by 1L chemotherapy regimen and analysis of overall survival (OS) from start of 1L chemotherapy.
Authors: Srikala S. Sridhar, Thomas Powles, Shilpa Gupta, Miguel Ángel Climent, Jeanny B. Aragon-Ching, Cora N. Sternberg, Paul Cislo, Nuno Costa, Alessandra Di Pietro, Joaquim Bellmunt, Petros Grivas
Journal: Journal of Clinical Oncology (2023)

508 Background: For platinum-eligible patients (pts) with advanced UC, 1L cisplatin- or carboplatin-based chemotherapy regimens followed by avelumab maintenance in pts without progression has become the standard of care. This is based on the results of the phase 3 JAVELIN Bladder 100 trial (NCT02603432), which showed significantly longer OS and progression-free survival (PFS) from start of maintenance (randomization) with avelumab maintenance + best supportive care (BSC) vs BSC alone (median OS, 23.8 vs 15.0 months; HR, 0.76 [95% CI, 0.63-0.91]; p=0.0036). We report post hoc analyses of long-term outcomes by 1L chemotherapy regimen and OS from start of 1L chemotherapy. Methods: Pts with unresectable locally advanced or metastatic UC that did not progress with 4-6 cycles of 1L cisplatin + gemcitabine or carboplatin + gemcitabine were randomized 1:1 to receive avelumab + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS measured from randomization. Secondary endpoints included PFS and safety. Results: At data cutoff (June 4, 2021), median follow-up from randomization was ≥38 months in both arms. In subgroups treated with 1L cisplatin + gemcitabine or carboplatin + gemcitabine, OS and PFS (measured from start of maintenance [randomization]) were longer in the avelumab + BSC arm than in the BSC alone arm (Table). Safety findings were similar in both subgroups. In the overall population, median OS measured from the start of 1L chemotherapy was 29.7 months (95% CI, 25.2-34.0) in the avelumab + BSC arm and 20.5 months (95% CI, 19.0-23.5) in the BSC alone arm (HR, 0.77 [95% CI, 0.635-0.921]). Conclusions: Long-term follow-up from the JAVELIN Bladder 100 trial confirms that avelumab 1L maintenance provides similar OS and PFS benefits in pts with advanced UC who are progression free following standard-of-care 1L cisplatin- or carboplatin-based chemotherapy, with an acceptable safety profile. The median OS measured from start of chemotherapy further supports the use of avelumab 1L maintenance as standard of care in this setting and provides a benchmark for future clinical trials. Clinical trial information: NCT02603432 . [Table: see text]
Dynamic and immunocytochemistry analysis of circulation tumor cells (CTCs) in blood samples from patients with advanced ccRCC starting first-line treatment in a Brazilian Cancer Center.
Authors: Milena Shizue Tariki, Anna Paula Carreta Ruano, Jacqueline Aparecida Torres, Alexcia Camila Braun, Daniela JF Costa, Giovana Tardin Torrezan, Dirce Maria Carraro, Walter Henriques da Costa, Ludmilla T.D. Chinen
Journal: Journal of Clinical Oncology (2023)

704 Background: Treatment of advanced clear cell renal carcinoma (ccRCC) improved dramatically in the last 20 years, but biomarkers development lagged behind. Circulating tumor cell (CTC) is used as a prognostic and predictive tool in many solid tumors but is poorly studied in ccRCC. Objective: Our aim was to evaluate CTC counts in serial blood samples from patients with advanced ccRCC that started first-line treatment and analyze the protein expression of PBRM1, BAP1, PD-L1 and CD133 in these cells. Methods: Blood samples (10mL) were collected in EDTA tubes at three different timepoints, 30 days apart, after treatment start. We used a filtration technique (ISET system, Rarecells/France) to isolate and collect CTCs. Protein expression was evaluated by immunocytochemistry. Results: Twelve patients were included. All had detectable CTCs at baseline (1st blood draw), with a median of 1.5 CTCs/mL. Patients with CTCs above the median had ≥2 metastatic sites (p=0.015) and worse progression free survival (PFS) (19.7 vs 31.1 months, p=0.35), although the difference was not statistically different. Favorable CTCs kinetics at the time of first follow-up (2nd blood draw) indicated better PFS (24.76 months) versus unfavorable (6.65 months; p=0.014). PBRM-1, BAP-1 and PD-L1 expression in CTCs was associated with better overall survival (OS), although without statistical significance. CD133 expression in CTCs at baseline was associated with worse OS (p=0.08). Conclusions: CTCs isolation was feasible in advanced ccRCC patients starting first-line treatment and were frequently detected by ISET method. CTC counts at baseline and at 30 days after treatment initiation had prognostic implication, as well as its dynamic evaluation after 30 days of treatment with a favorable kinetics associated with better outcome.
Exploratory analysis of predictive biomarkers for immune-related adverse events (irAEs) due to checkpoint inhibitors (CPIs) in patients with genitourinary (GU) cancers.
Authors: Elham Vosoughi, Dalia Kaakour, Wen-Pin Chen, Nataliya Mar
Journal: Journal of Clinical Oncology (2023)

569 Background: CPIs targeting PD-1/PD-L1 and CTLA-4 have transformed management of GU cancers. These agents are associated with a unique type of immune-mediated toxicities that may affect any organ, which may be severe or life-threatening. Development of irAEs may in part depend on type of CPI used, type of solid tumor, and individual patient factors including presence of subclinical inflammatory states. However, distinct biomarkers predictive of irAE development are poorly defined. This study aimed to examine possible associations between tumor mutation burden (TMB) and PD-L1 expression with occurrence of irAEs. Methods: A retrospective chart review was performed of all patients with urothelial carcinoma (UC) and renal cell carcinoma (RCC), who received therapy with CPIs from 1/2019 to 9/2022 at our institution and developed associated irAEs. Severe irAEs were defined as those necessitating initiation of immunosuppressive therapies or other supportive therapies. TMB and PDL-1 expression patterns were analyzed, if available. Given lack of standardized cutoffs for PD-L1 positivity across different GU cancer types, tumors were considered positive if a combined positive score of greater than 10 was present in UC or a total positive score of greater than 1% was present in RCC. Results: A total of 60 patients were included in this analysis - 33 with UC and 27 with RCC. Severe irAEs occurred in 19 patients with UC and 25 patients with RCC. Median TMB was 8.7 in patients with UC, while it was 2.5 in patients with RCC. PD-L1 positivity was seen in 39.3% (13/33) of UC patients and 40.7% (11/27) of RCC patients. In the UC cohort, 57.8% (11/19) had severe irAEs and TMB less than 10, while 36.8% (7/19) had severe irAEs and TMB greater than 10. Further, 47.3% (9/19) of UC patients had severe irAEs and positive PD-L1, while 42.1% (8/19) had severe irAEs and negative PD-L1. In the RCC cohort, 88% (22/25) had severe irAEs and TMB less than 10, while 8% (2/25) had severe irAEs and TMB greater than 10. Additionally, 40% (10/25) RCC patients had severe irAEs and positive PD-L1, while 56% (14/25) had severe irAEs and negative PD-L1. The incidence of TERT promoter mutations and TMB is noted in the table. Conclusions: Identification of predictive biomarkers of irAEs from CPIs is a major area of need in GU malignancies. Definitive conclusions from this dataset are limited by its small sample size. Interestingly, there appear to be differences in baseline expression of traditional immune biomarkers between UC and RCC, with lower prevalence of TMB greater than 10 and positive PD-L1 noted in the RCC cohort. As such, their utility when making treatment decisions in clinical practice may be of limited value. [Table: see text]
Real-world survival outcomes of patients (pts) treated with 6-weekly pembrolizumab 400mg (pem6w) plus axitinib (axi) for advanced renal cell carcinoma (aRCC).
Authors: Sonam Ansel, Mark Stares, Robert J. Jones, Stefan N. Symeonides, Laura Manson, Anirban Ray-Chaudhuri, Manreet Randhawa, Sarah Slater, Abeera Devasar, Jahangeer Malik, Aravindhan Sundaramurthy, Tony Elliott, Balaji Venugopal
Journal: Journal of Clinical Oncology (2023)

645 Background: The Keynote 426 trial demonstrated 3-weekly pembrolizumab 200mg (pem3w) plus axi twice daily is effective in aRCC. We previously reported real-world experience of pem6w + axi demonstrating a comparable safety profile to pem3w + axi reported in Keynote 426, with the added benefit of less frequent hospital visits. Here we present updated results on progression free survival (PFS) and landmark analyses of overall survival (OS) at 6, 9 and 12-months. Methods: Electronic medical records of pts on pem6w + axi between 1st May 2020 &amp; 1st June 2021 in two large cancer centres in Scotland were analysed retrospectively for pts’ characteristics, efficacy and treatment related adverse events (TRAE). A data cut-off of 1 st June 2022 was applied. Results: A total of 93 pts were identified (baseline demographics previously reported). 74 pts (80%) had clear cell histology, 19 pts (20%) had non-clear cell and 11 pts (12%) had sarcomatoid component. Approximately half had previous nephrectomy (46 pts). 15 (16%), 46 (50%) and 32 (34%) pts respectively were classified as favourable, intermediate, and poor risk group as per international metastatic renal cell carcinoma database consortium (IMDC) criteria. The median follow-up was 13 months (inter-quartile range [IQR] 8-17). At data cut off, 59 (63%) had progressed or died, with median PFS of 10.7 (IQR: 4.6-not reached) months. At landmark time-points of 6, 9 and 12 months 63 (68%), 50 (54%) and 42 (45%) of pts were progression free (Table). The median OS was not reached and follow up continues. At landmark time-points of 6, 9 and 12 months 88 (95%), 69 (74%) and 65 (70%) of pts were alive (Table). Clinician assessed radiological response was evaluable in 87 pts. Overall response rate (ORR), including partial response and complete response, was noted in 51 pts (59%). Clinical benefit rate including pts with ORR and stable disease was seen in 74 pts (85%). 82 pts (88%) had any grade and 28 pts (30%) had grade 3/4 TRAE. Any grade immune related AE (irAE) occurred in 62 pts (67%) and grade 3/4 in 19 pts (20%); g3/4 transaminitis (10%), colitis (8%), nephritis (2%) and skin (2%). Any grade AE due to axi occurred in 69 (74%) and grade 3/4 AE in 14 pts (15%). 25pts (27%) on Pem and 19pts (20%) on axi discontinued treatment due to TRAE. Conclusions: Our real-world experience demonstrates that pem6w + axi appears to have comparable efficacy and safety profile to pem3w + axi reported in Keynote 426 study. [Table: see text]
Is transrectal ultrasound or magnetic resonance imaging better at estimating prostatic volume for patients with prostate cancer?
Authors: Maxwell Sandberg, Wyatt Whitman, Anita Rong, Ronald Davis, Ashok Hemal, Matvey Tsivian
Journal: Journal of Clinical Oncology (2023)

314 Background: Determining the correct size (volume) of the prostate is imperative for patients with prostate cancer. Prostate size can affect many parameters in patient care such as cores in a biopsy taken and available treatment options. Traditionally, most patients underwent transrectal ultrasound (TRUS) during prostate biopsy to estimate prostatic volume. While TRUS is still used to estimate prostate volume, more recently prostate Magnetic Resonance Imaging (MRI) has also come into favor. Current literature indicates MRI is more accurate than TRUS for prostate size, but few studies exist, and whether differences in the two are clinically significant remains uncertain. The purpose of this study was to compare prostate volumes from TRUS and MRI to gross specimens after prostatectomy. Methods: Patients who underwent radical prostatectomy for prostate cancer between 2017–2022 were identified. TRUS and MRI measurements closest to the date of surgery were obtained. These were compared to gross prostate specimens after surgery, which was considered the gold standard. All TRUS volumes were recorded by a urologist during prostate biopsy using the ellipsoid formula (L*W*H*(π/6)). MRI measurements were done by a radiologist also using the ellipsoid formula. The weight and dimensions of gross specimens were measured by a pathologist. Ellipsoid formula was then used to calculate final volume measurements in gross specimens. Paired samples t-test was used to compare averages of TRUS and MRI to the gross specimen. Results: 83 patients were included in the study with an average age at prostatectomy of 65.47 years. TRUS volume significantly differed from gross specimen volume by an average of –4.56 mL (p=0.017) and gross specimen weight by -14.31 g (p &lt;0.001). MRI volume was not significantly different from gross specimen volume, by an average of –0.56 mL (p=0.771) and was significantly different from prostate weight by –10.32 g (p &lt;0.001). When compared to one another, TRUS and MRI significantly differed on average by –4 mL (p=0.033). Conclusions: MRI is more accurate than TRUS to estimate prostate volume. Both MRI and TRUS underestimate prostate weight. Urologists should be aware of potential inaccuracies when assessing preoperative prostate volume with TRUS, and recognize MRI is the best predictor of size. While imperfect, TRUS is still relatively accurate measuring prostate volume, and given its ease of availability and cost, we feel it is a useful modality to determine prostate size. [Table: see text]
The Lung Immune Prognostic Index (LIPI) stratifies prognostic groups and correlates with gut microbiota (GM) in patients with advanced renal cell carcinoma (RCC).
Authors: Carolina Alves Costa Silva, Silvia Zoppi, Anna Reni, Gianmarco Piccinno, Imran Lahmar, Luigi Cerbone, Lucía Carril-Ajuria, Emeline Colomba, Ronan Flippot, Cissé Sow, Nicola Segata, Bernard Escudier, Laurence Zitvogel, Laurence Albiges, Lisa Derosa
Journal: Journal of Clinical Oncology (2023)

719 Background: The LIPI score has been reported as an independent prognostic factor in RCC patients treated with immune checkpoint inhibitors (ICI) or tyrosine kinase inhibitors (TKI). Here, we aimed to correlate LIPI score and GM composition in patients with RCC. Methods: We prospectively collected fecal samples of all comers RCC patients who started a 1 st or beyond line therapy (standard or clinical trial) in the NCT0457446 at Gustave Roussy. Neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) were obtained from routine blood tests. Shot gun metagenomic sequencing (MGS) data were analyzed by multivariate and pair-wise/fold ratio . Clinical benefit ratio (CBR, complete response + partial response + stable disease, RECIST1.1) and overall survival (OS, from treatment start) were evaluated. Multivariate analysis (MVA) for OS included age, gender, therapy line, IMDC, histology, hypoalbuminemia. Results: From February 2016 to July 2021, 160 patients were screened and 102 were included. Median age was 61 years (22-89), patients were mostly males (75%) and clear cell histology (90%). Patients were treated in 1 st (15%), 2 nd (53%) and beyond (32%) lines. Treated with ICI monotherapy (65%), followed by TKI or mTOR (20%) and ICI combination (19%). IMDC was 32% good (G), 54% intermediate (I) and 14% poor (P) and LIPI was 69% G, 25% I and 6% P. Median OS was 42.9, 17.7 and 8.3 months in patients with LIPI G, I and P, respectively (p&lt;0.0001) . Among IMDC risk groups, IMDC G + LIPI G had better OS compared to other subgroups (p=0.017), and those with IMDC P + LIPI P had the worse OS. Overall, LIPI G had higher rates of CBR than I+P LIPI (74% vs 50%; p=0.0158). At MVA, LIPI was independently associated with OS (HR 6.25, 2.02-24.34; p=0.0187). Overall, Parabacteroides merdae and Veillonella parvula were enriched in LIPI I+P, while LIPI G harbored Faecalibacterium prausnitzii. In patients treated with ICI monotherapy, LIPI I+P were enriched with Bacteroides spp ( P. merdae, Phocaeicola vulgatus), and LIPI G had an overrepresentation of Ruminococcaceae unclass bacterium. Conclusions: We report the first MGS study correlating LIPI score and GM composition in RCC patients. LIPI score correlates with clinical outcomes (OS and CBR) and helped to better-stratified IMDC risk groups. Patients LIPI G harbor health-related commensals, while I and P groups are associated with harmful ones. LIPI score could represent a clinically relevant score to stratify mRCC patients. Clinical trial information: NCT04567446 .
Real-world outcomes in patients with metastatic renal cell carcinoma (mRCC) receiving dual immune checkpoint inhibitor (ICI-ICI) regimens or immune checkpoint inhibitor and tyrosine kinase inhibitor (ICI-TKI) combinations as first-line therapy: A British Columbia (BC) population-based analysis.
Authors: Antoine Morin Coulombe, Faisal Abdullah Alsadoun, Xin (Cynthia) Ye, Maryam Soleimani, Lucia Nappi, Bernhard J. Eigl, Kim N. Chi, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2023)

646 Background: Currently available first-line treatment regimens for mRCC include pembrolizumab-axitinib (ICI-TKI) and ipilimumab-nivolumab (ICI-ICI). Although both regimens are superior to sunitinib, direct comparisons between ICI-ICI and ICI-TKI are lacking and real-world data are sparse. Methods: Through BC Cancer pharmacy data and patient access programs queries, we identified 319 mRCC patients who were treated with first line ICI-TKI or ICI-ICI between May 2019 and March 2022. Patients’ charts were reviewed for baseline characteristics, including International mRCC Database Consortium (IMDC) risk criteria, pharmacy data, pathology and radiology reports, treatment toxicity, rationale for treatment choice when available, progression and survival outcomes. Treatment groups were compared using standard descriptive statistics; survival outcomes were compared using Kaplan Meier and Cox Regression analyses. Results: Among the first 214 patients, 64.9% and 35.1% received first line ICI-ICI and ICI-TKI, respectively. The most commonly cited reason for choosing ICI-ICI was unavailability of a publicly funded alternative at the time of prescription. IMDC risk group distribution was markedly different between regimens; in ICI-TKI patients, favorable, intermediate and poor-risk patients respectively represented 60.3%, 28.8% and 10.9%, versus 10.2%, 56.9% and 32.9% in ICI-ICI patients (p&lt;0.001). Response rates in ICI-TKI compared favorably to ICI-ICI in the overall population with objective response rates (ORR) of 69% vs 50.4% (p=0.012) and primary progression rates of 12.7% vs 33.1% (p=0.001). However, in the intermediate-poor risk patients, survival outcomes were similar between ICI-TKI and ICI-ICI, with median progression-free survival (mPFS) of 7.5 versus 4.5 months respectively (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.41 to 1.09, p=0.107) and median overall survival (mOS) of not reached (NR) vs 22.6 months (HR 0.86, 95% CI 0.44 to 1.69, p=0.665). Of interest, in patients treated with ICI-ICI, more ipilimumab infusions in the induction phase was associated with improved mOS, rising from 3.9 to 13.6, 21.8 and 37.5 months for 1, 2, 3 or 4 infusions respectively (statistically significant by Log Rank [Mantel-Cox], p&lt;0.001). Conclusions: In the real-world mRCC experience from BC, Canada, ICI-TKI was associated with statistically significantly improved ORR over ICI-ICI although the treated population was comparatively enriched for favorable risk patients by IMDC. PFS and OS did not differ between the two regimens in the intermediate-poor risk population. Updated results on all 319 patients will be presented.